Long-term maintenance of therapeutic cyclosporine levels leads to optimal graft survival without evidence of chronic nephrotoxicity

Since the introduction of cylcosporine into clinical use, a major area of concern within the transplant community has been the fear of chronic nephrotoxicity. Although progressive renal damage does appear to occur in native kidneys of heart and liver transplant patients receiving cyclosporine, it has been our contention that its use is not a major cause of deterioration in renal allografts. We therefore undertook a study of 91 consecutive renal transplants performed over a three-year period with a minimum graft survival of 1 year and a follow-up of 7–9 years. Serial serum creatinine values, iothalamate clearances and cyclosporine levels were obtained at 3 months after transplantation and yearly thereafter. Biopsies were performed on all grafts that had failed as well as on the majority of patients with deteriorating renal function, and were interpreted by two nephropathologists. As measured by iothalamate clearances, 65 % of the patients in this series exhibited absolutely stable renal function despite the maintenance of cyclosporine levels of more than 200 ng/ml for 7–9 years. Since these stable patients did not reveal any decline in renal function, it therefore follows that they did not experience chronic cyclosporine nephrotoxicity. Furthermore, none of the patients with declining renal function or with failed grafts showed any evidence of nephrotoxicity on biopsy. Chronic cyclosporine nephrotoxicity may be a cause of declining function or graft loss with renal transplant recipients, but if so, it is exceedingly rare. Received: 17 March 1998 Received in revised form: 8 October 1998 Accepted: 18 December 1998     

Renal Responses to exercise in heart and kidney transplant patients

There is a lack of information about renal responses in heart and kidney transplant patients after intense physical exercise. Eleven heart and ten kidney transplant recipients, as well as two control groups of healthy subjects, were given a maximum exercise test on a bicycle ergometer. One control group was also given a moderate load corresponding to the peak load of the kidney transplant group. Blood and urine samples were collected before and after exercise and assayed for lactate, creatinine, total protein, and albumin. The glomerular filtration rate remained stable at the end of exercise in the transplant patients, while there was a slight (17 %) decrease in the control group. Albumin excretion rates after maximum exercise attained a mean of 237 μg · min^–1in the control group and a mean of 45 and 16 μg · min^–1, respectively, in the heart and kidney groups. Postexercise proteinuria seemed to be related to the absolute intensity of the event, but kidney transplant patients showed a reduced effect as compared to heart transplant patients. We conclude that short-term, maximum exercise in heart and kidney transplant recipients is not detrimental to kidney function. Received: 21 November 1996 Received after revision: 4 March 1997 Accepted: 18 March 1997     

Angiotensin-II receptor antagonist losartan reduces microalbuminuria in hypertensive renal transplant recipients

In recent years, it has been demonstrated that losartan lowers macroproteinuria in diabetic or non-diabetic renal transplant recipients (RTx) similar to angiotensin converting enzyme (ACE) inhibitors. Microalbuminuria (MAU) may reflect subclinical hyperfiltration damage of the glomerulus. It could be a marker of kidney dysfunction in renal transplantation. The aim of the study was to assess the efficacy of losartan in hypertensive RTx with MAU. This study was conducted in 17 (M/F: 4/13) stable RTx. No change was made in the medical treatment of the patients. All cases received 50 mg/day losartan therapy for 12 wk. Renal functions and MAU were determined 12 and 6 wk and just before the treatment as well as sixth and twelfth week of the treatment in all patients. Losartan satisfactorily lowered systemic blood pressure. A significant reduction in MAU was observed from 103 +/- 53 microg/min at the beginning to 59 +/- 25 microg/min in the sixth week and 47 +/- 24 microg/min in the twelfth week (p=0.0007 and 0.0005, respectively). From the sixth week of the treatment, the therapy significantly decreased hemoglobin, hematocrit and erythrocyte levels but did not change mean leukocyte and platelet counts, urea, creatinine levels and creatinine clearances. No serious side-effect was observed during the study. In conclusion, we found that losartan decreased MAU in hypertensive RTx. For that reason, it might be considered as the first choise antihypertensive agent for the renoprotection in selected patients.     

Permanently reduced plasma ionized magnesium among renal transplant recipients on cyclosporine

Hypomagnesemia is common after kidney transplantation. Until recently, only the determination of total plasma magnesium was possible, whereas the assessment of ionized magnesium has since become practicable. One hundred and nine renal transplant patients on cyclosporine with allografts functioning stably for more than 6 months and plasma creatinine levels of less than 200 μmol/l entered the study. Total and ionized circulating magnesium were assessed among these 109 patients, as well as among 15 renal transplant patients not on cyclosporine and 21 healthy volunteers. Cyclosporine patients showed significantly lower total and ionized circulating magnesium values than the two control groups. Plasma total and ionized magnesium levels were also significantly lower among cyclosporine patients treated concurrently with insulin or oral hypoglycemic agents than among those who were not. No correlation was noted between time after transplantation and plasma magnesium with respect to patients on cyclosporine. In conclusion, the study demonstrates that a large subset of renal transplant patients treated with cyclosporine have permanent deficiencies of ionized and total magnesium. The tendency towards hypomagnesemia is also more pronounced among patients with diabetes mellitus. Received: 28 May 1998 Received after revision: 27 November 1998 Accepted: 18 December 1998     

Frequency of mucosal HPV DNA detection (types 6/11, 16/18, 31/35/51) in skin lesions of renal transplant patients

Human papillomaviruses (HPV) probably play a role in the development of skin cancer in renal transplant recipients. Since some mucosal HPV are strongly related to cervical cancer, we compared the frequency of HPV DNA detection (mucosal types 6/11, 16/18, and 31/33/51) in skin cancer of renal transplant recipients (21 lesions) with that in normal subjects without immunodeficiency (21 lesions) and studied the frequency of these same HPV in benign lesions of renal transplant recipients (34 lesions) and normal subjects (30 lesions). An in situ hybridization technique employing cold biotin probes was used. HPV DNA was not significantly (P = 0.095) more frequent in malignant skin cancer in renal transplant recipients (42.9 %) than in normal subjects (19.04 %), but was significantly more frequent in benign lesions in renal transplant recipients (32.4 %) than in controls (10 %; P < 0.05). These results on a limited number of skin lesions do not allow one to confirm the predominant role of mucosal HPV in the development of skin cancer in renal transplant recipients. HPV interaction with other factors related to the immunosuppressive state may play a role. Received: 21 May 1996 Received after revision: 6 September 1996 Accepted: 28 October 1996     

Atypical mycobacterium infection with dermatological manifestation in a renal transplant recipient

In April 1997, a 58-year-old renal transplant recipient presented with abscess-like nodules in his left calf and on his right foot. Furuncular disease was suspected and the patient was treated with flucloxacillin. However, the lesions increased in size and became ulcerative. In the following 3 months, cultures of punctuated material, blood, and urine remained negative and gram stains did not reveal micro-organisms. In June 1997, acid-fast stains were positive. A diagnosis of a nontuberculous mycobacterium (NTM) infection was made and empirical antimycobacterial therapy was started. The combination of relatively minor symptoms with enlarged purulent lesions, causing severe morbidity, raises the possibility of NTM infection in the immunocompromised patient. Received: 24 March 1998 Received after revision: 28 July 1998 Accepted: 23 September 1998     

Anemia due to losartan in hypertensive renal transplant recipients without posttransplant erythrocytosis

Losartan is a safe, effective long-term treatment for hypertension or posttransplant erythrocytosis (PTE) in renal transplant recipients. There were only a few studies in patients without PTE and their results were different. Starting from week 6 and continuing to the week 12 we observed a decrease in hemoglobin (Hb) and hematocrit (Hct) levels in patients without PTE. Anemia developed in 42.8% of the patients, and Hb levels increased after the withdrawal of losartan treatment. There was a significant decrease in Hct levels beginning from week 3 when compared with the control group. Our study suggests that losartan therapy can decrease Hb beyond its antihypertensive efficacy. Based on the capacity of losartan to decrease Hb and Hct, this drug should be carefully used in patients with preexistent anemia or low Hb levels.     

Better microvascular function on long-term treatment with lisinopril than with nifedipine in renal transplant recipients.

BACKGROUND: The prevalence of hypertension in renal transplant recipients is high but the pathophysiology is poorly defined. Impaired endothelial function may be a factor of major importance. The present study addresses the effects of long-term treatment with either lisinopril or slow-release nifedipine on microvascular function and plasma endothelin in renal transplant recipients on cyclosporin A (CsA). METHODS: Seventy-five hypertensive renal transplant recipients were double-blind randomized to receive slow-release nifedipine (NIF, n=40) or lisinopril (LIS, n=35). Ten normotensive, age-matched recipients served as controls. All patients received CsA-based immunosuppressive therapy including prednisolone and azathioprine. Microvascular function was assessed in the forearm skin vasculature, using laser Doppler flowmetry in combination with post-occlusive reactive hyperaemia and endothelial-dependent function during local acetylcholine (ACh) stimulation. RESULTS: The analysis of microvascular function (AUC(rh)) showed that nifedipine-treated patients had significantly lower responses compared with lisinopril-treated patients (20+/-17 and 43+/-20 AU x min respectively, P=0.0016). Endothelial function was borderline significantly lower in the NIF group compared with the LIS group (640+/-345 and 817+/-404 AU x min respectively, P=0.056). The responses in the LIS group were comparable with those in non-hypertensive controls (AUC(rh) was 37+/-16 and AUC(ACh) was 994+/-566 AU x min). Plasma endothelin-1 concentrations were significantly higher in the NIF group compared with the LIS group (0.44+/-0.19 vs. 0.34+/-0.10 fmol/ml respectively, P=0.048), and were 0.29+/-0.09 fmol/ml in the control patients. AUC(ACh) was associated with plasma endothelin-1 (P=0.0053), while AUC(rh) was not (P=0.080). CONCLUSIONS: The study indicates that long-term treatment with lisinopril, when compared with nifedipine, yields a more beneficial effect on microvascular function in hypertensive renal transplant recipients on CsA. The beneficial microvascular effect may be mediated in part by an endothelin-1-associated effect on the endothelium.     

Post Transplant Erythrocytosis in Hypercalcemic Renal Transplant Recipients

In vitro data suggest that calcium plays an important role in normal and disordered erythropoiesis. The purpose of this study is to determine whether there is an association between serum calcium, various hormone levels, and the development of post transplant erythrocytosis (PTE). Data were collected on 283 patients who underwent renal transplantation between 1994 and 1998. The relationship between serum calcium and PTE development was tested using the chi-square test. Univariate and multivariable adjusted models were employed to determine predictors of maximum hematocrit. Selected patients underwent measurement of intact parathyroid hormone (PTH), 1,25-dihydroxy vitamin D, and erythropoietin (EPO). Seventy-three patients (26%) developed PTE. Post transplant erythrocytosis was more common in patients with hypercalcemia compared with patients with normal serum calcium (34% vs. 18%, p = 0.002). In multivariable analyses, serum calcium was a strong independent predictor of maximum hematocrit post transplant, even after adjustment for renal function. A serum calcium of >or=10.2 mg/dL was associated with greater than two-fold increased odds of PTE. There were no differences in hormone levels between subjects with hypercalcemia and PTE, subjects with PTE alone, and subjects with hypercalcemia alone. Hypercalcemia is associated with the development of PTE in renal transplant recipients.     

Intravenous ganciclovir prophylaxis for cytomegalovirus in heart, heart-lung, and lung transplant recipients

Cytomegalovirus (CMV) disease has had a significant clinical impact on the heart, heart-lung and lung transplant recipients in our centre. CMV disease has been so severe with CMV antibody-negative heart-lung transplant patients receiving organs from CMV antibody-positive donors (CMV-mismatched patients) that in 1986 we adopted the policy of not transplanting CMV-positive organs into CMV-negative heart-lung or lung recipients. In December 1992, we instituted a policy of providing intravenous ganciclovir (5 mg/kg twice a day for 28 days) during the immediate postoperative period for CMV-mismatched heart recipients and CMV antibody-positive heart-lung and lung patients, who have been the patients at greatest risk of severe CMV disease in our centre. A placebo group was not employed because of ethical considerations, ganciclovir having been shown to be effective for the treatment of CMV infections among transplant patients. Compared with a historical control group of patients receiving no prophylaxis, prophylactic ganciclovir reduced the incidence of CMV infection (39 % vs 91 %, P = 0.0006) and CMV disease (17 % vs 74 %, P = 0.0004) among CMV antibody-positive heart-lung recipients. Prophylactic ganciclovir did not significantly reduce the incidence of CMV infection or disease among heart or isolated lung recipients. Ganciclovir was well tolerated, with few adverse reactions. In the case of heart-lung transplant patients, one month of intravenous prophylactic ganciclovir significantly reduced the incidence of both CMV infection and disease when compared with patients who received no prophylaxis. With the lung transplant and heart transplant patients, there were no significant differences between the prophylaxis and nonprophylaxis groups, although there was a consistent trend towards less infection and disease in the prophylaxis groups. Received: 14 April 1998 Received after revision: 24 September 1998 Accepted: 18 December 1998     

Factors Associated with Hyperhomocysteinemia After Renal Transplantation

Recent studies show that clinically stable renal transplant recipients have an increased prevalence of hyperhomocysteinemia (hyperHcy), but the mechanism of this disorder has not yet been elucidated. The aim of the present study was to evaluate the factors associated with hyperHcy after a successful renal transplantation. In 106 stable renal transplant recipients, total serum Hcy level (tHcy), folate, total protein, serum creatinine concentration, creatinine clearance, lipid status, body weight (BW), body mass index (BMI), and body fat (BF) were determined. The mean doses of cyclosporine, prednisolone, and azathioprine (mg/kg/day) were recorded. The mean serum tHcy level was significantly higher in renal transplant patients than in healthy controls (22.02 ± 8.02 versus 13.0 ± 3.3 μmol/L; p < 0.001), and the incidence of patients with hyperHcy was 82%. Comparison of the group of 20 patients with tHcy level <15 μmol/L and the group of 86 patients with tHcy level >15 μmol/L revealed that the latter was significantly older, heavier, had been longer on dialysis before renal transplantation, and had older donors and poorer renal graft function. Significant correlation was found between tHcy level and recipient age, dialysis duration, BW, creatinine clearance, serum creatinine, and folate concentration. However, multivariate analysis indicated that creatinine clearance (p = 0.025) and BW (p = 0.03) were the only determinants of elevated total Hcy level in renal transplant recipients. HyperHcy persists after successful kidney transplantation in the majority of renal transplant recipients, and its appearance is primarily associated with creatinine clearance and body weight.     

Clinical characteristics of normotensive renal transplant recipients with microalbuminuria and effects of angiotensin II type I receptor antagonist on urinary albumin excretion

AIM: Microalbuminuria is typically observed in renal transplant recipients with systemic hypertension. The effects of angiotensin II type 1 receptor antagonist (losartan) on the hypertensive recipients have been evaluated. However, the clinical background of normotensive recipients with microalbuminuria and the effect of losartan administration in those subjects have not been clarified. One of the two purposes for the present study was to investigate the clinical characteristics of normotensive recipients with microalbuminuria. The other was to evaluate the effect of losartan on urinary excretion of albumin in these patients. METHODS: The clinical data and the change of the single kidney glomerular filtration rate (GFR) for the graft by radionuclide study were assessed in 13 normotensive recipients with microalbuminuria. These were compared with the data of 13 normotensive patients without microalbuminuria. The 13 recipients with microalbuminuria were treated with losartan for one year and urine excretion of albumin, N-acetyl-beta-D-glucosaminidase (NAG) and serum creatinine (S-Cr) levels were measured. RESULTS: The GFR of the grafts from donors to recipients significantly increased (30.9 to 55.2 mL/min) in microalbuminuric recipients, but did not significantly increase in the non-microalbuminuric recipients. Decreases of the urinary excretion rate of albumin (351 +/- 261 at baseline to 158 +/- 14 mg/gCr at 12 months), NAG (13 +/- 5 to 10 +/- 3 IU/gCr) and S-Cr (1.7 +/- 0.6 to 1.5 +/- 0.4 mg/DL) were observed in the microalbuminuric recipients with losartan administration. CONCLUSIONS: The present study suggests that an increased single kidney GFR of the graft from the donor in situ to the recipient might be a cause of microalbuminuria in normotensive recipients. The one-year effects of losartan were observed in terms of the decrease in urinary excretion of albumin, NAG and S-Cr levels.     

Campylobacter jejuni bacteremia and Guillain-Barré syndrome in a renal transplant recipient

In patients who have not undergone transplantation, Guillain-Barré syndrome (GBS) is typically preceded by an acute infection often sustained by Campylobacter jejuni. Thus far, in renal transplant recipients, only eight cases of GBS have been reported. In seven patients GBS was attributed to cytomegalovirus infection and in the eighth patient to cyclosporin A neurotoxicity. We report here the case of a GBS in a renal transplant recipient following C. jejuni bacteremia. The infection quickly disappeared after erythromycin and methronidazole therapy. GBS progressively evolved into a paraparesis within 1 week. After reaching a plateau phase, the clinical status improved and the patient was able to walk unassisted after 3 weeks. At his last check-up, 54 months later, the patient was doing well with a functioning graft and only minimal weakness of the lower limbs. Received: 17 February 1998 Received after revision: 7 July 1998 Accepted: 8 July 1998     

Successful transplantation of organs retrieved from a donor with enterococcal endocarditis

We report on a patient with an extensive cerebral infarction secondary to enterococcal endocarditis that, in spite of adequate antibiotic treatment, evolved to brain death. The patient was evaluated as a potential organ donor; renal and liver function were normal and both liver and kidneys appeared normal on ultrasonographic examination. When negativity of serial blood and urine cultures was ascertained, liver and kidneys were retrieved for transplantation. The organs were transplanted into three recipients with good results after 14 months of follow-up. All of the recipients received antibiotic prophylaxis against Enterococcus faecalis. None of them has presented infectious complications to date. This case emphasizes that patients with enterococcal endocarditis may be potential organ donors provided both donor and recipients are adequately treated. This is especially important when organs are urgently needed. Received: 3 February 1998 Received after revision: 24 March 1998 Accepted: 15 April 1998     

Circulating interleukin-1 receptor antagonist (IL-1RA) serum levels in patients undergoing orthotopic heart transplantation

In a pilot study we determined the serum levels of circulating interleukin-1 receptor antagonist (IL-1ra) in patients undergoing orthotopic heart transplantation and in control patients scheduled for open heart surgery without allograft transplantation. Blood samples were obtained from 12 transplant recipients and 7 controls prior to the operative procedures to determine baseline values. Serum levels of IL-1ra were measured within 12 h of decrossclamping of the aorta and every 24 h for the following 14 days. Endomyocardial biopsies were obtained weekly for the 1st month after transplantation. Compared to baseline values, IL-1ra serum levels 12 h after decrossclamping of the aorta were significantly higher both in the control group (507 ± 165 vs 3980 ± 452 pg/ml, P < 0.01) and among the transplant recipients (413 ± 180 vs 4117 ± 459 pg/ml, P < 0.01) IL-1ra levels remained significantly elevated for 2 and 5 days, respectively. There were no significant differences in the IL-1ra serum levels between the two groups throughout the observation period. Endomyocardial biopsies of two patients showed acute allograft rejection, Billingham grade III a and III b, respectively. In both cases, the rejection episodes were accompanied by a renewed and more pronounced elevation in the IL-1ra serum levels beyond 4000 pg/ml for at least 2 days. These preliminary results indicate that IL-1ra may be a nonspecific immune marker during the first few days after orthotopic heart transplantation and cardiopulmonary bypass. Moreover, renewed, prolonged increases in IL-1ra appear to be associated with rejection. Further studies are needed to confirm the predictive value of IL-1ra in the detection of acute allograft rejection. Received: 26 May 1998 Received after revision: 21 August 1998 Accepted: 21 August 1998     

Successful Surgical Treatment of Renal Cell Carcinoma in a Transplanted Kidney from a Cadaveric Donor: Report of a Case

Posttransplant renal cell carcinoma (RCC) usually arises in the native kidneys of renal transplant recipients rather than in the transplanted kidney. This report describes a case of RCC that developed in the transplanted cadaveric kidney in a 37-year-old male recipient 9 months after transplantation. An en bloc radical transplant nephrectomy was performed, and he has subsequently remained stable on hemodialysis for 3 years without any sign of recurrence. Received: March 27, 2000 / Accepted: September 26, 2000     

Factors affecting the therapeutic response of enalapril in treatment of post transplant erythrocytosis

Summary: Enalapril was used for post transplant erythrocytosis (PTE) in 19 stable male hypertensive renal allograft recipients. Post transplant erythrocytosis was defined as haematocrit (Hct) >0.45 for 3 consecutive months. Dosage of enalapril was adjusted according to the blood pressure of individual patients and varied from 2.5 mg to 20 mg per day in divided doses. Patients'serum creatinine level, blood pressure and haematocrit were monitored. Therapeutic response was expressed as percentage drop in Hct (Δ%Hct). Factors affecting Δ%Hct was then determined. After 32 weeks of treatment, haematocrit fell from 0.495 ± 0.021 to 0.396 ± 0.053, which represented a 19.9% drop (paired Student's t-test, P > 0.001). With multiple regression analysis, reciprocal of plasma creatinine (RCr) prior to enalapril therapy (B = 3.40 ± 0.72, P > 0.0005), dose of enalapril adjusted with bodyweight (B = - 0.058 ± 0.020, P > 0.02, and pre-treatment haematocrit level (B = - 1.90 ± 0.71, P > 0.02) were found to be independent factors affecting Δ%Hct. We concluded that the dosage of enalapril, renal allograft function and severity of erythrocytosis were the major factors affecting the therapeutic response of PTE by enalapril treatment.     

Disappearance of hepatitis B virus core deletion mutants and successful combined kidney/liver transplantation in a patient treated with lamivudine

Hepatitis B virus (HBV) core deletion variants with enhanced viral replication are associated with rapid deterioration of liver function in renal allograft recipients. Antiviral agents such as famciclovir and lamivudine offer new treatment strategies for these patients. Appearance, accumulation and persistence of HBV core deletion mutants were closely monitored in a kidney transplant recipient with liver cirrhosis before and after initiation of antiviral treatment. Under treatment with famciclovir HBV DNA concentration decreased by 50 %, HBV mutants persisted. After replacement of famciclovir by lamivudine HBV replication was reduced below the detection limit. Lamivudine was well tolerated and liver function improved. After successful combined kidney/liver transplantation the patient became HBsAg and HBV DNA (detected by PCR) negative under continuous hyperimmune globulin and lamivudine treatment. Antiviral therapy with lamivudine may be useful in treatment of progressive liver disease associated with HBV core deletion mutants in renal allograft recipients and may enable successful liver transplantation. Received: 12 June 1998 Received after revision: 16 October 1998 Accepted: 10 November 1998     

肾移植与血液透析治疗对尿毒症患者阴茎勃起功能影响的临床对照研究

目的:研究对比男性尿毒症患者接受肾移植与接受血液透析治疗勃起功能的变化及与生殖激素水平变化的关系。方法:收集2009年5月至2012年1月在我院门诊进行随访的肾移植男性患者35例、血液透析治疗的尿毒症患者30例,应用国际勃起功能指数(IIEF-5)调查表、夜间勃起功能(NEVA)测定仪评估阴茎勃起功能,同时测定生殖激素水平。结果:接受肾移植手术者勃起功能障碍(ED)患病率为51.4%,血液透析者ED患病率为73.3%(P<0.05);肾移植后的ED患者发病情况要明显轻于单纯血液透析的ED患者;肾移植中重度ED患者(25.7%)要明显少于单纯血液透析者(46.6%);肾移植组中ED患者夜间阴茎勃起次数、勃起强度及持续时间均强于单纯血液透析组ED患者(P<0.05);接受肾移植患者较单纯血液透析血清睾酮水平上升[(4.32±1.37)vs(2.53±1.12)ng/ml,P<0.05],雌二醇[(19.57±2.29)vs(43.38±5.58)pg/m)]和催乳激素[(8.59±1.19)vs(17.22±3.31)mIu/ml]明显下降(P均<0.05)。结论:肾移植受者肾功能良好时其总体勃起功能要优于单纯血液透析的尿毒症患者。     

Long-term,prolonged-release tacrolimus-based immunosuppression in de novo kidney transplant recipients: 5-year prospective follow-up of the ADHERE study patients

The objectives of this study were to assess long-term graft survival, patient survival, renal function, and acute rejections in de novo kidney transplant recipients, treated with once-daily prolonged-release tacrolimus-based therapy. The study was a 5-year non-interventional prospective follow-up of patients from the ADHERE study, a Phase IV 12-month open-label assessment of patients randomized to receive prolonged-release tacrolimus in combination with mycophenolate mofetil (MMF) (Arm 1) or sirolimus (Arm 2). From 838 patients in the randomized study, 587 were included in the long-term follow-up, of whom 510 completed the study at year 5. At 1 year post-transplant, graft and patient survival rates were 93.0% and 97.8%, respectively, and at 5 years were 84.0% and 90.8%, respectively. Cox proportional hazards analysis showed no association between graft loss, initial randomized treatment arm, donor age, donor type, or sex. The 5-year acute rejection-free survival rate was 77.4%, and biopsy-confirmed acute rejection-free survival rate was 86.0%. Renal function remained stable over the follow-up period: mean ± SD eGFR 4-variable modification diet in renal disease formula (MDRD4) was 52.3 ± 21.6 ml/min/1.73 m² at 6 months and 52.5 ± 23.0 ml/min/1.73 m² at 5 years post-transplant. These findings support the role of long-term once-daily prolonged-release tacrolimus-based immunosuppression, in combination with sirolimus or MMF, for renal transplant recipients in routine clinical practice.